tbuckley/cabot-search huggingface dataset:
Abstract 14182: A Missense Mutation in Ryanodine Receptor 2 Leads to Structural Remodeling of the Heart and Cardiac Arrhythmia in a Rabbit Model
Authors: Jingjing Zheng, Holly Dooge, Hector Valdivia, Francisco Alvarado
Journal: Circulation (2022)

Ryanodine receptor 2 (RyR2) is the Ca 2+ release channel of sarcoplasmic reticulum that provides the majority of Ca 2+ necessary for contractions of the heart. RyR2 mutations are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disorder with normal heart structure. There are reports suggesting that RyR2 mutations can also lead to structural heart disease, notably arrhythmogenic right ventricular cardiomyopathy (ARVC); however, additional research is required to support this association. We generated a rabbit model carrying the missense mutation RyR2-V2475F, linked to CPVT in humans. Heterozygous (V2475F +/- ) rabbits show a CPVT-like syndrome and display arrhythmia under pharmacological stress. Homozygotes (V2475F +/+ ) show a stronger phenotype, with 37% of the animals (13/35) experiencing sudden death at 22.5±3.8 weeks old during regular housing. Remarkably, gross examination of V2475F +/+ hearts showed significant structural remodeling, characterized by fibrous infiltrations and thinning of the right ventricle with or without left ventricle involvement. This phenotype is reminiscent of ARVC. Lead II ECG obtained in conscious rabbits by telemetry showed that V2475F +/+ animals have significant bradycardia (144.6±11.1 bpm) with prolonged QT interval (QTc: 180.4±8.2 ms, n=6) compared to WT (HR: 224.9±4.2 bpm, p=0.04; QTc: 157.4±5.3 ms, p=0.02, n=5). After subcutaneous injection of 0.5 mg/kg of isoproterenol, WT rabbits showed the expected positive chronotropic response (HR, 367±10 bpm, n=3) while V2475F +/+ animals developed bouts of ventricular tachycardia. Mild emotional stress applied by transporting the animal around the laboratory, also induced ventricular arrhythmia in 100% (5/5) V2475F +/+ rabbits, while WT littermates were unaffected. RyR2-V2475F expressed in a rabbit model triggers remarkably different phenotypes based on the zygosity of the animals, ranging from a purely arrhythmogenic syndrome (CPVT) in V2475F +/- animals to severe structural disease compatible with ARVC in V2475F +/+ rabbits. The RyR2-V2475F rabbit model is therefore an excellent model to dissect the intersection of arrhythmic and structural phenotypes due to RyR2 dysfunction.
Abstract 13587: A Prior History of Myocarditis Increases Risk of COVID-19-Related Myocarditis
Authors: ALI VAELI ZADEH, Alan Wong, Ashvin Zachariah, Elias Collado, Joshua Larned
Journal: Circulation (2022)

Background: Viral myocarditis (MC) is an uncommon inflammatory condition of the myocardium. Its pathogenesis is postulated to involve a combination of direct virus-induced cardiomyocyte injury and immune-mediated cell death that results in fibrosis, dilated cardiomyopathy, arrhythmias, and heart failure. Studies indicate an increased incidence of MC in association with COVID-19 infection. However, the risk factors for COVID-19-related MC remain unknown or debated. This study sought to examine the association between a prior history of MC and COVID-19- related MC. Methods: Using ICD-10 codes, a cohort of patients admitted between March-August 2020 with the primary diagnosis of COVID-19 was identified from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). The cohort was divided into two groups based on prior history of all-cause MC. To determine the incidence of MC, both groups’ records were searched in the 60-day period after admission. We used Pearson's chi-squared test to compare the MC frequencies between groups. Results were reported as Risk Ratios (RR) with 95% CI. A p-value &lt;0.05 was deemed significant. Results: We identified 439,172 admissions with COVID-19. Of this cohort, 914 (0.208%) had at least one episode of MC before admission. Patients with a history of MC were younger (mean age 56, SD 19 vs. 60, SD 16), mostly male (54%), with more comorbidities (Elixhauser Comorbidity Index = 9 vs. 6) . Two months after hospitalization, 756 (0.17%) of COVID-19 patients developed MC. The risk of MC was 8.31% among patients with a history of MC and 0.16% among those without. The risk of COVID-19-related MC was significantly higher in patients with a prior history of all-cause MC (RR = 53.59, 95% CI = 42.66-67.31, p&lt;0.0001) Discussion: According to our findings, patients with a history of MC are significantly more likely to develop COVID-19-related MC. A proposed mechanism could be that previously injured cardiomyocyte may be expressing higher levels of ACE2, which allows SARS-CoV-2 to enter. Our results help in risk stratification based on a history of MC.
Abstract 14156: Termination of Atrial Fibrillation During Ablation Predicts Long-Term Success
Authors: Nektarios Vasilottos, Awaneesh Kumar, Cody McCoy, Tanyanan Tanawuttiwat, John M Miller, Mithilesh Das
Journal: Circulation (2022)

Background: The predictive value of termination of atrial fibrillation (AF) during catheter ablation (CA) during a long-term follow-up is not known. Methods: We studied the predictive value of AF termination (spontaneous or induced) during ablation in patients who underwent CA of persistent and paroxysmal AF and followed them for recurrence of AF/atrial flutter (FL). Results: Of 187 patients (male: 75%, mean age: 60.3 ± 10.7 years) who underwent CA of AF, 65 (34.8%) patients had termination during the initial CA. A mean number of 1.4 ± 0.6 ablations were performed during follow-up in both groups. There were no significant differences in baseline characteristics including age, gender, race, body mass index, left ventricular ejection fraction, and presence of hypertension, diabetes, and valvular disease. During a median (±1SE) follow-up of 5.23 ± 0.17 years, a significantly higher percentage of patients who had termination during CA were in sinus rhythm as compared to patients who did not have termination during CA (87.6 vs 63.1%, p &lt; 0.001). Cox regression analysis confirmed termination of AF during ablation as a predictor of whether the patient was in sinus rhythm at time of last follow-up (OR: 0.24, 95% CI 0.09 to 0.62, p = 0.003). Kaplan-Meier survival analysis shows significantly decreased time to recurrence in patients who did not have AF termination than patients who had AF termination during CA. Conclusion: The present study identifies termination of AF during CA as a predictor of successful ablation during 5-year follow-up.
Abstract 12914: Effect of Home-Based versus Center-Based Cardiac Rehabilitation Among Attendees From a Large Healthcare System During the Covid-19 Pandemic
Authors: Audry Chacin Suarez, Tomoaki Hama, Thomas G Bissen, Amanda R Bonikowske, Haddijatou Jallow, Michael J Rogers, Abigail L Ryskey, Rosalyn M Salstrand, Robert Scales, Adam M Shultz, Joshua R Smith, Kara A Sweere, Bryan J Taylor, Courtney Wheatley-Guy, Thomas P Olson
Journal: Circulation (2022)

Introduction: The COVID-19 pandemic imposed significant constraints to delivery of cardiac rehabilitation (CR) with many programs relying on delivery of home-based cardiac rehabilitation (HBCR). We sought to compare the effects of HBCR vs conventional center-based CR (CBCR) on clinical metrics, health-related quality of life, and modifiable risk factors in CR patients. Methods: Retrospective cohort study comparing 511 HBCR patients (March 2020-April 2021; COVID-19 pandemic) and 765 age and sex matched CBCR patients (Jan 2018-Jan2020; immediately pre-pandemic) from the Mayo Clinic Health System. We assessed changes in clinical outcomes before and after CR. HBCR included 12 sessions (one in-person assessment + weekly education and exercise monitoring phone/video calls). Conventional CBCR included 36 sessions (3 sessions per week for 12 weeks). Continuous data were described as mean±SD, and comparisons of change between groups were assessed with linear regression adjusting for baseline value, in complete cases. Results: HBCR and CBCR patients were 65±14 yrs old (68% male) and 65±14 yrs old (67% male) respectively. HBCR patients demonstrated greater improvement in exercise days/week whereas CBCR patients had greater improvement in exercise min/day. HBCR patients had greater improvement in blood glucose with a trend towards greater improvement in non-HDL cholesterol. Both groups demonstrated similar improvement on nutrition, depression, health-related quality of life surveys and total, LDL and HDL cholesterol, as well as HbA1c between the groups. Conclusions: Collecting clinical metrics during the COVID-19 pandemic proved challenging due to the initial closure of out-patient services. For patients in whom data was captured, HBCR appears to be similarly effective at improving several intermediate outcomes compared to CBCR. HBCR may be an effective alternative for improving clinical outcomes in patients who are unable to participate in CBCR.
Abstract 13: Myocardial Metabolic And Electrolyte Derangements Linked To PEA Rearrest
Authors: Laken Irish, Bisan Abboud, Lydia Akino, Soufian Almahameed, Ohad Ziv, Steven Poelzing, Joseph S Piktel, Kenneth R Laurita, Lance D Wilson
Journal: Circulation (2022)

Background: Cardiac rearrest after return of spontaneous circulation (ROSC) is a significant barrier to successful resuscitation, making it a high priority for emergency care research. Regardless of initial arrest rhythm, rearrest is commonly due to pulseless electrical activity (PEA). However, mechanisms underlying PEA rearrest are poorly understood. Previously, myocardial contractile function during ischemia-reperfusion has been tied to alterations in extracellular sodium (Na+) and calcium (Ca2+) concentrations. Objective: To determine physiological predictors and explore potential mechanisms underlying susceptibility to PEA rearrest. Methods: Acute myocardial infarction (AMI) induced by left anterior descending artery (LAD) occlusion was followed by 8 min of VF, then pigs were resuscitated (defibrillation, CPR, epinephrine) to ROSC and the LAD was reperfused. Pigs were instrumented to measure metabolic variables from arterial and coronary sinus venous blood gases, electrolytes, and hemodynamics. Subjects that had PEA rearrest (n=7) were compared to those that did not rearrest (n=4). Results: Hemodynamic and primary arrest characteristics were similar between PEA and no rearrest groups, including ischemia duration, time to ROSC, CPR events, and epinephrine administration. At ROSC, hemodynamic and metabolic variables including pH, myocardial lactate consumption, myocardial arterial/venous oxygen difference were also similar between groups. Importantly, post-ROSC myocardial lactate consumption was significantly increased in the PEA group (3.9 vs. 0.5 mmol, p&lt;0.03) as was coronary sinus Na+ (147 vs. 135 mEq/L, p&lt;.03); however, coronary sinus Ca2+ was significantly reduced (1.9 vs. 2.3 mEq/L, p&lt;.01 ). Taken together, these data suggest that metabolic substrate depletion may promote local electrolyte shifts contributing to mechanical dysfunction underlying PEA. Conclusion: PEA rearrest was associated with increased myocardial lactate consumption and derangements in cardiac Na+ and Ca2+ in a translational model with well controlled arrest characteristics. Improved understanding of mechanisms underlying post-ROSC electrolyte shifts may identify novel mechanisms and therapeutic approaches to prevent and treat PEA.
Abstract 14401: A Rare Case of Patent Foramen Ovale Thrombus Caught in Transit
Authors: Rupinder Buttar, Devesh Rai, Ritambhara Pandey, Mohan Rao, bipul baibhav
Journal: Circulation (2022)

Introduction: Patent foramen ovale (PFO), seen in about 20-25% of the population, is linked with paradoxical embolism. However, a paradoxical thrombus seen in transit through a PFO is an extremely rare finding. Case: An 80-year-old-female with a history of stroke, atrial fibrillation (AF), and diabetes presented with a complaint of dizziness. She had a history of non-compliance with her anticoagulation for AF. EKG showed AF with rapid ventricular rate. An echocardiogram showed a large mobile thrombus in both atria representing a paradoxical embolus in transit caught in PFO (Figure A). Right ventricular systolic function was noted to be severely reduced. A transesophageal echocardiogram confirmed a paradoxical embolus in transit with a large amount of mobile thrombus in the left atrium (Figure B, C). Large saddle acute pulmonary embolus, extending bilaterally into main, lobar, and segmental pulmonary arteries, was seen on the CT chest (Figure D). Lower extremity ultrasound revealed right popliteal vein thrombosis extending to the peroneal vein. Due to a high risk of paradoxical systemic embolism patient underwent emergent surgical thrombectomy along with the closure of PFO. Conclusion: Paradoxical thrombus in transit through PFO carries a high risk of systemic embolism. Therapeutic options for patients include cardiac surgery with thrombectomy, thrombolysis, or systemic anticoagulation, with no clear consensus regarding the best treatment option.
Abstract 14225: Atrial Tachycardias After Surgical Left Atrial Appendage Exclusion
Authors: Lucas Rich, Amrish Deshmukh, Ryan Cunnane, Rakesh Latchamsetty, Thomas Crawford, Aman Chugh, Fred Morady, Matthew A Romano, Hakan Oral
Journal: Circulation (2022)

Introduction: Surgical left atrial appendage exclusion (LAA-Ex) is often performed to eliminate the need for long-term anticoagulation either as a stand-alone or concomitant procedure during cardiac surgery. A modified MAZE procedure is also usually performed during surgical LAA-Ex. Residual arrhythmogenic foci within the LAAA and/or zones of slow conduction along the stump of the LAA may contribute to recurrent atrial tachycardias (AT) after LAA-Ex. The purpose of this study was to determine the role of the LAA in recurrent atrial tachycardias (ATs) after surgical LAA-Ex. Methods: Catheter ablation (CA) was performed to eliminate ATs in 21 patients with history of AF (persistent in 18/21, 86%) 25±26 months after surgical LAA-Ex. There were 3 women; mean age was 66±9 years; and the left atrial diameter was 54±8 mms. A concomitant MAZE procedure and CA was performed previously, in 16 and 9 patients, respectively. Two patients had neither maze nor catheter ablation. There was residual blood flow into the LAA in 1/21 patient. Results: A reentrant AT involving the stump of the LAA was identified in 5/21 (24%) patients. Focal ablation on a critical isthmus within a zone of slow conduction along the LAA stump terminated AT in 3/5 patients. In the remaining 2 patients a linear lesion set from the stump to an existing line of block (left atrial roof line and anterior mitral annulus) terminated the macroreentrant AT revolving around the LAA stump. During 16±13 months of follow-up 10/21 patients (48%) remained free from recurrent ATs without antiarrhythmic drug therapy. A repeat ablation was performed in 3 patients, the mechanism of the AT was epicardial, perimitral, and multifocal but did not involve the LAA. Conclusions: After surgical LAA-Ex recurrent ATs are not uncommon and can involve the LAA stump, Although these ATs can be successfully identified and ablated, other ATs may recur and prompt additional antiarrhythmic or ablative therapy.
Abstract 13963: Short-Coupled Variant of Torsade de Pointes: A Rare Entity With Unknown Etiology and Malignant Phenotype
Authors: suraj krishnan, Juan F Torrado, Gustavo Duarte, Qussay Marashly, andrew krumerman
Journal: Circulation (2022)

Introduction: Torsade de Pointe (TdP) is defined as a polymorphic VT (pVT) typically associated with QTc prolongation. However, not all pVT occur in the presence of QTc prolongation and respond to different forms of therapy. Hence defining their etiology is important. Case: A 48-yo Female with H/O resolved peripartum cardiomyopathy, hypertension &amp; obesity presented to the hospital following a syncopal episode. Her BP was 207/125 mmHg, and ECG showed sinus rhythm with a QTc of 436. No history of heart disease or SCD in her family. Physical exam was unremarkable, labs showing K-3.2 without troponin elevation. On day 2, she developed a pVT requiring defibrillation and amiodarone. Telemetry revealed a PVC causing R on T phenomenon with a coupling interval of 260 msec prior to initiation of SVT with QTc 484 and K-2.8. On day 3, despite electrolyte correction, she had multiple non-sustained pVTs with QTc 482. Amiodarone was switched to lidocaine and QTc normalized to 447. TTE and LHC were unremarkable with a small LV aneurysm on cMRI. On day 4, the patient continued to have incessant runs of pulseless pVT requiring defibrillation and started on verapamil. A 12 lead ECG during VT demonstrated left bundle branch mimicry with a left axis consistent with a VT exit site along the RV moderator band. The patient underwent emergent ablation with targets along the right anterolateral papillary muscle. AICD was placed prior to discharge. Discussion: The critical timing of PVC falling on the peak of the preceding T wave differentiates ‘Short-coupled TdP’ from other malignant VTs with normal QTc. These PVCs typically originate from distal ramifications of Purkinje fibers in both ventricles. PVC morphology with LBBB pattern, left axis and late precordial R-S transition points to the moderator band as the source of idiopathic VT. Contrasting with typical TdP, medical management with Quinidine and Verapamil may be efficacious. Catheter ablation is curative in most cases.
Abstract 13769: AT1R Autoantibody Levels Are Elevated in Patients Who Required Immunosuppression Escalation in Immune Checkpoint Inhibitor Mediated Myocarditis
Authors: Narjes Akhlaghi, Miles Shen, Laurine Bow, Maureen Miller, John Hwa, Stephanie Halene, Lauren A Baldassarre, Jennifer M Kwan
Journal: Circulation (2022)

Intro: Angiotensin-II (Ang-II) plays an important role in the pathophysiology of various cardiovascular disorders, including cardiomyopathy and hypertension. Angiotensin II type 1 receptor (AT1R) mediates the deleterious effects of Ang-II and can cause vasoconstriction, vascular and cardiac remodeling, and cell death. Animal models have shown that the AT1R signal is obligatory for the development of virus-induced myocardial injury through the proinflammatory action of Ang-II. Data from animal studies and human case studies showed AT1R autoantibodies (AT1R A) were a novel mediator of vasomotor changes and LV dysfunction related to acute myocarditis and that blocking AT1R can be effective. Hypothesis: Little is known whether patients on immune checkpoint inhibitors (ICI) develop AT1R A and whether this can worsen the severity of ICI myocarditis. We measured AT1R A in 9 hospitalized patients who were diagnosed with ICI induced myocarditis. We describe this cohort, the course of their illness and their response to steroids. Methods: This was a prospective study. Quantitative antibodies to AT1R at the time of hospitalization were measured by an Enzyme Linked Immunosorbent Assay (ELISA) (One Lambda) and classified as positive (&gt;17U/mL); at risk (10-17 U/mL) and negative (&lt;10 U/mL). Results: Demographic and co-morbidity details are shown (Table 1). 5/9 patients (55%) were either positive or at risk for AT1R A elevation. 4/9 patients (45%) were AT1R A negative. 4/5 (80%) of the AT1R A positive/at risk required increased immunosuppression whereas 1/4 (25%) of the AT1R A negative required increased immunosuppression for myocarditis. Conclusions: AT1R autoantibodies may worsen the severity of ICI myocarditis. A larger cohort study and comparisons of AT1R A levels in non-ICI patients are underway. If trends hold true, testing for AT1R A and treating with an angiotensin receptor blocker may be a potential strategy to reduce ICI myocarditis severity.
Abstract 13042: Circulating Obesity Associated Pro-Fibrotic Protein as a Brown Adipokine Promotes Liver and Heart Fibrosis in Obese Nash Mice
Authors: Yung-ting Hsiao, Ippei Shimizu, Yohko Yoshida, Tohru Minamino
Journal: Circulation (2022)

Introduction: Non-alcoholic steatohepatitis (NASH), driven by the obesity epidemic, has become the most common form of liver disease. Excessive calorie intake inflames visceral adipose tissue, and let this organ produce pro-inflammatory adipokines. Brown adipose tissue (BAT) is another type of fat pad equipped with the thermogenic capacity, and the role of BAT-derived adipokines (BATokines) in pathogenesis of NASH remains to be explored. Hypothesis: Various kinds of white adipokines are known in obesity. However, BATokines in pathogenesis of NASH still remain to be explored. Methods: To identify the function of obesity associated pro-fibrotic protein (OAFP), we generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and murine OAFP knockout (KO) model. We also conducted functional in vitro studies with differentiated brown adipocytes. Results: Here we identified a secreted type pro-fibrotic protein OAFP, as one of the BATokines contributing for the promotion of liver fibrosis in a murine NASH model. We also found that OAFP increased in circulation of human NASH patients. Genetic models with OAFP suppression ameliorated liver fibrosis, in contrast, OAFP gain of function model enhanced this in our NASH model. In addition, we found that cardiac fibrosis also developed in the NASH model, and this was ameliorated in OAFP-KO model, indicating the pathogenic role of OAFP in heart failure with preserved ejection fraction (HFpEF). Our biobank studies also showed OAFP increased in HFpEF patients. We also found ER stress-mediated signaling enhanced the production of this BATokine. Conclusions: Our results testing mice models, and human studies indicate suppression of OAFP becomes therapies for HFpEF and NASH.